The goals of this research are: investigation of factors of erythrocyte membrane structure and cellular shape which determine cell rheology with correlation of those rheologic properties of normal and pathologic cells with their behavior in capillaries and microvascular systems of spleen and muscle. Specific objectives include: 1. study of the effects of pH, osmolarity, physiologic hormones and drugs known to affect cell shape and membrane elasticity, and intracellular ATP, Ca ions, and Mg ions relationships with the endofacial surface of membrane; 2. exploration of specific mechanisms resulting in altered membraned ion permeation; characterization of capillary flow of normal and pathologic cells in glass microcapillaries, model microcirculatory systems comprising multichamber filters and vascular replicas of organs (e.g., spleen) and in vivo capillaries of skeletal and cardiac muscle, to determine oxygen delivery to muscle cells in the presence of senescent and sickle erythrocytes; and investigate mechansims of capillary obstruction by sickle and senescent erythrocytes and endothelial injury. Techniques include separation of erythrocyte proteins and lipids to study factors determining protein polymerization and significance to membrane elasticity, and to reconstitute membranes to relate structure to strength; use of inside-out membrane vesicles and ghosts to determine effects of spectrin properties, ATP and Ca binding on ion permeability, distensibility and viscoelasticity; determination of membrane mechanochemical properties is achieved by measurement of stress-strain and area compressibility responses and observation of capillary flow in vitro and in animal skeletal muscle capillaries by microscopy-video recording techniques. Measurement of capillary intraluminal pressures is accomplished by servonulling techniques and velocity recorded by correlated dual diode responses. pH, pO2 data from arterial wall, microvessels and tissues will be monitored by specific microelectrodes. Electron microscopy will be used to characterize cell capillary interaction and adherence.